The Orexin System. Basic Science and Role in Sleep Pathology

Description

The orexin system, discovered in 1998, has emerged as a crucial player in regulating the sleep and wake balance inside our brain. This discovery has sparked a burst of novel and dynamic research on the physiology and pathology of sleep. The Orexin System: Basic Science and Role in Sleep Pathology honors this research and the authors share their ideas and perspectives on the novel developments within the field. The book examines the intricate role of the orexin system in regulating sleep and wake, and its interaction with other wake-regulating systems. The orexin system is dissected at the cellular and molecular level to explore the diversity of the orexin-producing neurons, their projections, and their signaling pathways. Additionally, the book discusses the diseases which are associated with a dysfunctional orexin system, such as narcolepsy, insomnia, substance abuse, and Alzheimer’s disease, and explores the new potential therapeutic applications derived from the burst of research around this fascinating system. This publication is essential reading for neurobiologists, neurologists, psychopharmacologists, sleep researchers, and other researchers and clinical scientists interested in sleep, sleep research, insomnia, and medicine in general.

Informations

• Publié par: S. Karger AG
• Date de parution: 28 mai 2021
• Nombre de lectures: 0
• EAN13: 9783318068443
• Langue: English
• Poids de l'ouvrage: 7 Mo

Extrait

Frontiers of Neurology and Neuroscience

TheOrexinSystem. Basic Science and Role in Sleep Pathology

Editors Michel A. Steiner Masashi Yanagisawa Martine Clozel

Volume 45

The Orexin System. Basic Science and Role in Sleep Pathology

Frontiers of Neurology and Neuroscience Vol. 45

Series Editor J. Bogousslavsky Montreux

The Orexin System. Basic Science and Role in Sleep Pathology

Volume Editors

M.A. Steiner Allschwil M. Yanagisawa Tsukuba M. Clozel Allschwil

20 figures, 19 in color, and 5 tables, 2021

Basel ∙ Freiburg ∙ Hartford ∙ Oxford ∙ Bangkok ∙ Dubai ∙ Kuala Lumpur ∙ Melbourne ∙ Mexico City ∙ Moscow ∙ New Delhi ∙ Paris ∙ Shanghai ∙ Tokyo

Frontiers of Neurology and Neuroscience Vols. 1–18 were published as Monographs in Clinical Neuroscience

Dr. Michel A. Steiner Idorsia Pharmaceuticals Ltd CH–4123 Allschwil (Switzerland) [e-mail]

Prof. Masashi Yanagisawa International Institute for Integrative Sleep Medicine (WPI-IIIS) University of Tsukuba Tsukuba, Ibaraki 305-8575 (Japan) [e-mail]

Library of Congress Cataloging-in-Publication Data

Names: Steiner, M.A. (Michel-Alexander), editor. | Yanagisawa, M. (Masashi), editor. |  Clozel, M. (Martine), editor. Title: The orexin system : basic science and role in sleep pathology /  volume editors, M.A. Steiner, M. Yanagisawa, M. Clozel. Other titles: Frontiers of neurology and neuroscience ; v. 45. 1660-4431 Description: Basel ; Hartford : Karger, 2021. | Series: Frontiers of  neurology and neuroscience, 1660-4431 ; vol. 45 | Includes  bibliographical references and indexes. | Summary: “Discovered in 1998,  the orexin system lies at the core of the sleep and wake state  regulation inside our brain. This book summarizes recent research, ideas  and perspectives from some of the most influential researchers in the  fields of hypocretin/orexin and sleep. For example, it explains the  intricate role of the orexin system in the different sleep phases and in  the pathways that are related to memory and cognition. It also provides  an overview of diseases which are caused by, or associated with a  dysfunctional orexin system, such as narcolepsy, insomnia, substance  abuse, or Alzheimer’s disease”-- Provided by publisher. Identifiers: LCCN 2021007426 (print) | LCCN 2021007427 (ebook) | ISBN  9783318068436 (hardcover ; alk. paper) | ISBN 9783318068443 (ebook) Subjects: MESH: Orexins--physiology | Sleep--physiology | Orexin  Receptors--physiology | Wakefulness--physiology | Sleep Wake  Disorders--physiopathology Classification: LCC QP572.O74 (print) | LCC QP572.O74 (ebook) | NLM W1  MO568C v.45 2021 | DDC 612.4/05--dc23 LC record available at https://lccn.loc.gov/2021007426 LC ebook record available at https://lccn.loc.gov/2021007427

Dr. Martine Clozel Idorsia Pharmaceuticals Ltd CH–4123 Allschwil (Switzerland) [e-mail]

® Bibliographic Indices. This publication is listed in bibliographic services, including Current Contents and MEDLINE/Pubmed. Disclaimer. The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publisher and the editor(s). The appearance of advertisements in the book is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements. Drug Dosage. The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any change in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug. All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher. The authors, the editors, and the publisher have made every effort to obtain permission for all copyright-protected material. Any omissions are entirely unintentional. The publisher would be pleased to hear from anyone whose rights have unwittingly been infringed. © Copyright 2021 by S. Karger AG, P.O. Box, CH–4009 Basel (Switzerland) www.karger.com Printed on acid-free and non-aging paper (ISO 9706) ISSN 1660–4431 eISSN 1662–2804 ISBN 978–3–318–06843–6 e-ISBN 978–3–318–06844–3

The copyright of each individual book chapter is held by the author(s) of the respective chapter. Each individual chapter is licensed under a Creative Commons AttributionNonCommericalNo Derivative 4.0 International License (CC BYNCND 4.0). Any use of a book chapter in whole or in parts, in any way that is not covered by the applicable license, requires permission in writing by S. Karger AG.

Idorsia Pharmaceuticals Ltd and its affiliates have a license to use this work for their own commercial or promotional purposes.

Sponsor Note Idorsia Pharmaceuticals Ltd. supported the development of this volume of the Frontiers of Neurology and Neuroscience book series.

Disclosures The Guest Editors declare that during the development of the book, Michel A. Steiner and Martine Clozel were employed by Idorsia Pharmaceuticals Ltd., Allschwil, Switzerland, and that Professor Yanagisawa, an independent researcher (Director and Professor of the International Institute for Integrative Sleep Medicine [WPI-IIIS], University of Tsukuba, Ibaraki, Japan) received consultancy fees from Idorsia Pharmaceuticals Ltd.

Editorial assistance for the development of the book was provided by Jessica Beake (Beake Medicom), funded by Idorsia Pharmaceuticals Ltd.

V

Contents

IX  Preface  Steiner, M.A. (Allschwil); Yanagisawa, M. (Tsukuba); Clozel, M. (Allschwil)

Section I: The Orexin System and Its Role in Regulating Sleep and Wake  1  TwentyThree Years of Hypocretins: The “Rosetta Stone” of Sleep/  Arousal Circuits  de Lecea, L. (Stanford, CA) 11 between Orexin Neurons and Monoaminergic Systems Interaction  Sakurai, T.; Saito, Y.C.; Yanagisawa, M. (Tsukuba) 22 Receptor Pharmacology and Sleep Phases Hypocretin/Orexin  Sun, Y.; Tisdale, R.K.; Kilduff, T.S. (Menlo Park, CA) 38  Sleep, Orexin and Cognition  Toor, B.; Ray, L.B.; Pozzobon, A.; Fogel, S.M. (Ottawa, ON)

Section II: Cellular and Molecular Dissection of the Orexin System 52  Subsecond Ensemble Dynamics of Orexin Neurons Link Sensation and Action  Burdakov, D. (Zürich) 61 of Hypocretin/Orexin Neurons Heterogeneity  Sagi, D. (RamatGan); de Lecea, L. (Stanford, CA); Appelbaum, L. (RamatGan) 75 and Metabolism: Implication of Lateral Hypothalamic Neurons Sleep  Oesch, L.T.; Adamantidis, A.R. (Bern) 91 Signaling Mechanisms of Hypocretin/Orexin Cellular  Kukkonen, J.P.; Turunen, P.M. (Helsinki)

VI

Section III: The Orexin System in Sleep Pathology 103  Sleep Problems in Narcolepsy and the Role of Hypocretin/Orexin Deficiency  Mignot, E.; Zeitzer, J. (Palo Alto, CA); Pizza, F. (Bologna); Plazzi, G. (Bologna/Modena) 117  The InsomniaAddiction Positive Feedback Loop: Role of the Orexin System  Fragale, J.E.; James, M.H.; Avila, J.A. (Piscataway, NJ); Spaeth, A.M.; Aurora, R.N.  (New Brunswick, NJ); Langleben, D. (Philadelphia, PA); AstonJones, G. (Piscataway, NJ) 128  Causes and Consequences of Chronic Sleep Deficiency and the Role of Orexin  Mullington, J.M.; Cunningham, T.J.; Haack, M.; Yang, H. (Boston, MA) 139  Hypocretin/Orexin, Sleep and Alzheimer’s Disease  Dauvilliers, Y. (Montpellier)

150 Index Author 151  Subject Index

Contents

VII

Preface Published online: May 28, 2021

Steiner MA, Yanagisawa M, Clozel M (eds): The Orexin System. Basic Science and Role in Sleep Pathology. Front Neurol Neurosci. Basel, Karger, 2021, vol 45, pp IX–X (DOI: 10.1159/000514968)

Preface

Orexîns (ypocretîns) and teîr receptors were dîscovered în 1998. Orexîn neuropeptîdes are produced by a very small number of cells în te lateral ypotalamus, suggestîng a fundamental role în omeostasîs. Despîte te name “orexîn,” wîc was coîned after te orîgînal dîscovery of îts role în appetîte regulatîon, te orexîn system as foremost emerged as a crucîal player în te maîntenance of wakefulness and vîgîlance. Te orexîn system îs îgly conserved across vertebrates; îts role în arousal and wakefulness stabîlîzatîon îs es- sentîal and cannot be replaced by anoter braîn cîrcuît. Te dîscovery of ypocretîn/ orexîn rapîdly led to te ypotesîs of îts patogenîc contrîbutîon în te abnormal state of yperarousal of însomnîa and, for îts defîcîency, în narcolepsy and cataplexy. Sleep îs one of te greatest marvels and mysterîes of our pysîology. Sleep îs funda- mental to our daîly lîfe and te qualîty of our agîng. Sleep deprîvatîon alters learnîng and memory and îmmune cell actîvîty, încreases te rîsk of ypertensîon, cancer, and depres- sîon and încreases amyloîd- concentratîon în te braîn. Sleep elps to repaîr DNA strand breaks and synaptîc dîsruptîons tat occur durîng te actîve perîod and controls sympa- tetîc tone. Conversely, însomnîa îs a major dîsease în our modern world, and sleep îs îtself frequently affected by dîseases. Insomnîa îs one of te fîrst symptoms of Alzeîmer’s dîsease. Sort sleep duratîon predîcts îger all-cause mortalîty. Te dîscovery of te orexîn system opened te door to a novel and dynamîc researc on sleep. It îs tîs researc wîc we wîs to onor ere, wîtîn tîs book. Sînce tîs dîs- covery, parmaceutîcal companîes started to develop molecules to enance te under- standîng of te consequences of orexîn receptor blockade în însomnîa. In 2007, researc- ers at Actelîon Parmaceutîcals Ltd. descrîbed, for te fîrst tîme, te sleep-promotîng effects of a dual orexîn receptor antagonîst (DORA), almorexant, across several specîes, încludîng uman. In 2014 and 2019, respectîvely, te US Food and Drug Admînîstratîon (FDA) approved te two DORAs, suvorexant and lemborexant, for te treatment of prî- mary însomnîa. A tîrd molecule, darîdorexant, împroved not only sleep but also daytîme functîonîng în patîents wît însomnîa, and, as we publîs tîs book, îs under revîew for approval by ealt autorîtîes. Tese tree DORAs are all effîcacîous în reducîng latency to sleep and wake after sleep onset, and tey prolong total sleep tîme wîtout alterîng te pysîologîcal sleep arcîtecture.

hîs artîcle îs lîcensed under te Creatîve Commons Attrîbutîon-NonCommercîal-NoDerîvatîves 4.0 Internatîonal Lîcense (CC BY- NC-ND) (ttp://www.karger.com/Servîces/OpenAccessLîcense). Usage and dîstrîbutîon for commercîal purposes as well as any dîstrîbutîon of modîied materîal requîres wrîtten permîssîon.

Besîdes stabîlîzîng wakefulness, oter roles of orexîns are emergîng, încludîng te modulatîon of stress-, feedîng-, and reward-related patways wîtîn te braîn. Tîs functîonal dîversîty îs for a large part acîeved troug te complexîty of te orexîn sys- tem, wît îts two dîfferent peptîdes and two receptors tat are dîfferentîally released and dîstrîbuted trougout te braîn. Te fîrst selectîve orexîn 1 or 2 receptor antagonîsts (SORAs) ave entered clînîcal trîals and are currently under învestîgatîon for te treat- ment of mood, anxîety, and eatîng dîsorders. Orexîn receptor agonîsts are beîng ex- plored as novel treatments for narcolepsy. In tîs book,The Orexin System. Basic Science and Role in Sleep Pathology, we ave gatered te îdeas and perspectîves from some of te most înfluentîal researcers în te fîelds of ypocretîn/orexîn and sleep. As autors, tey sare teîr tougts on novel de- velopments and provîde focused revîews on topîcs of partîcular înterest. In te fîrst sectîon of te book, “Te Orexîn System and Its Role în Regulatîng Sleep and Wake,” Professors Luîs de Lecea, Takesî Sakuraî & Masasî Yanagîsawa, Tomas S. Kîlduff, and Stuart M. Fogel, take you on a journey to îllustrate te complexîty and înter- correlatîon of te orexîn system wît oter sleep- and wake-regulatîng neurotransmîtter systems. Te autors explaîn te întrîcate role of te orexîn system în te dîfferent sleep pases and în te patways tat are, for înstance, related to memory and cognîtîon. In te second sectîon, “Cellular and Molecular Dîssectîon of te Orexîn System,” Pro- fessors Denîs Burdakov, Lîor Appelbaum, Antoîne R. Adamantîdîs, and Jyrkî P. Kuk- konen, marvel at te cellular and subcellular dîversîty of te few tousand orexîn-produc- îng neurons wîtîn te ypotalamus. Te temporally controlled fîrîng of orexîn neurons and te spatîally restrîcted actîons wîtîn certaîn projectîon areas can be explaîned by te dîversîty în orexîn receptor sîgnalîng patways, te co-release of oter types of neu- rotransmîtters, te întegratîon of multîple încomîng sîgnals, and te assortments of dîf- ferent gene-expressîon profîles among clusters of orexîn neurons. In te fînal sectîon of te book, “Te Orexîn System în Sleep Patology,” Professors Emmanuel Mîgnot, Gary Aston-Jones, Janet M. Mullîngton, and Yves Dauvîllîers provîde an overvîew of dîseases wîc are caused by, or assocîated wît, a dysfunctîonal orexîn system, suc as narcolepsy, însomnîa, substance abuse, or Alzeîmer’s dîsease. Tey învîte us to explore te new potentîal terapeutîc applîcatîons derîved from researc around te orexîn system. We, as edîtors, wîs to acknowledge wît gratîtude te many scîentîsts, clînîcîans, and patîents wo ave contrîbuted towards te development of te understandîng of te orex- în system and te clînîcal applîcatîons to împrovîng te ealt of patîents and te com- munîty. We învîte te reader to now take a “deep dîve” înto te mysterîous world of tîs fascînatîng ypocretîn/orexîn system, wîc lîes at te core of te sleep and wake state regulatîon însîde our braîn. We ope you wîll fînd te capters as tougt-provokîng and înformatîve as we ave.

X

Michel A. Steiner, Allscwîl, Swîtzerland Masashi Yanagisawa, Tskukuba, Japan Martine Clozel, Allscwîl, Swîtzerland

Steiner/Yanagisawa/Clozel

Steiner MA, Yanagisawa M, Clozel M (eds): The Orexin System. Basic Science and Role in Sleep Pathology. Front Neurol Neurosci. Basel, Karger, 2021, vol 45, pp IX–X (DOI: 10.1159/000514968)